Drugs Targeting Nicotinic and Muscarinic Receptors Flashcards Preview

Describe cholinergic receptors

All cholinergic receptors bind ACh for activityThere are different types of cholinergic receptors, they are differentiated by their differing affinities for two agonists: nicotine and muscarineNicotinic: nicotinic ganglionic (also nicotinic neuronal) and nicotinic cholinergic (this is part of the somatic nervous system)Muscarinic: there are at least 5 subtypes of muscarinic receptors and all are GPCRs

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What happens with depolarization and neuromuscular junctions (NMJs)

What do depolarizing NMJ blockers do?

Depolarizing neuromuscular blockers (succinylcholine, decamethoium) initially can cause an action potential and propagate muscular contraction. But continued stimulus results in an increase in the resting membrane potential. Over time, continuous stimulation of Nm receptors increases the resting membrane potential resulting in the nearby voltage gated sodium channels becoming refractory and no muscular contraction is propagated

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How does a non depolarizing neuromuscular block work?

It is caused by competitive antagonism of the Nm receptor (d-tubocurarine and pancuronium)

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What are the uses of succinylcholine and pancuronium?

Although they work via different mechanism, both are used clinically to induce muscle relaxation during surgerySuccinylcholine is rapidly hydrolyzed by esterase's to inactive metabolites and is used when it is desirable to have tight control of blockade such as electroconvulsive therapy ECT for refractory depressionPancuronium is used for muscle relaxation during longer surgery procedures due to its longer duration of action

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What are examples of Ng selective antagonists?

TrimetaphanHexamethoniumNot used clinically anymore due to too many side effects

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M1 receptors: what type of G alpha protein do they interact with? What are the tissue locations? What are the cellular effects? What are their functions?

M3 receptors:what type of G alpha protein do they interact with? What are the tissue locations? What are the cellular effects? What are their functions?

They interact with G alpha q proteinsThey are found in the smooth muscle and the vascular endotheliumThey increase IP3 and DAG, intracellular calcium and decrease potassium outflow. Results: stimulationFunction: smooth muscle contraction

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Describe the conformational flexibility of acetylcholine

There is significant conformational flexibility in the ACh moleculeIt can adopt several conformations, some favour binding to nicotinic while others favour muscarinic receptorsWe can make restricted analogues and modify parts of the ACh structure to determine what parts of ACh are important for binding and what conformation ACh adopts when it binds to each receptor

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Why is ACh rapidly hydrolyzed by AChE?

Internal ion-dipole interaction with ACh increases polarization of carbonyl double bond. This carbonyl is a strong electrophile. At is very susceptible to hydrolysisThis is in part why it is rapidly hydrolyzed by AChE

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What is the difference between ACh and carbachol?

Delocalized electrons decrease the electrophilic nature of the carbonyl carbon. It resists hydrolysis by ACh

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What is the difference between ACh and methacholine?

Methyl-group is added as a "steric shield", which reduces access to carbonyl carbon by nucleophiles. It also streakily inhibits binding to AChE

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What is methacholine used for?

Used as a test for asthma called methacholine challenge test

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What is bethanechole used for?

Used to increase urinary outputOften after surgery or in prostatic hypertrophy that does not respond to conventional treatments like tamsulosin